Metabolic Syndrome
Metabolic syndrome {syn. syndrome X) is a complex disorder with high socioeconomic cost that is considered a worldwide epidemic. About 32% of people in USA are considered to suffer from metabolic syndrome, with the risk increasing with age (e.g., 40% of people aged between 40 and 60 are considered to suffer from this syndrome). Metabolic syndrome is associated with an increased risk of many disorders, such as, coronary heart disease, atherosclerotic disease, hypertension, stroke and type 2 diabetes. Currently, metabolic syndrome is diagnosed based on the presence of three or more of the following criteria:                Elevated waist circumference: definition of elevated depends on race, country and sex;        Elevated triglycerides: ≧150 mg/dL blood (1.7 mmol/L blood) or drug treatment for elevated triglycerides;        Reduced High density lipoprotein (HDL) cholesterol: <40 mg/dL blood (1.0 mmol/L blood) in men, <50 mg/dL blood (1.3 mmol/L blood) in women or drug treatment for low high density lipoprotein cholesterol;        Elevated blood pressure: systolic ≧130 mm Hg and/or diastolic >85 mm Hg or drug treatment for hypertension (or drug treatment for high blood pressure); and        Elevated fasting glucose: >100 mg/dL blood (or drug treatment for hyperglycemia)        
Current non-pharmacological therapies for metabolic syndrome include exercise and diet. Pharmacological treatments are generally targeted at one of the symptoms of metabolic syndrome. For example, compounds improving triglyceride and HDL levels have been suggested as useful for treating metabolic syndrome. However, these medications suffer from various undesirable side-effects. For example:                clofibrate (a fibric acid derivative) increases morbidity and mortality rates. Moreover, tumorigenicity has been demonstrated in rodents. Clinical trials have shown that some fibrates also cause reversible increases in serum creatinine levels.        Niacin has multiple adverse effects, the worst of which is chemical hepatitis. Other side effects include flushing, itching, and rash.        Statins are associated with muscle pain and rhabdomyolysis (which can lead to kidney failure and death), muscle weakness, neuropathy and memory loss. Furthermore, statins have a relatively short half life and require regular dosing to provide a therapeutic benefit. For example, atorvastatin has an effective half life of about 20-30 hours and in considered a long-acting statin.        
It will be apparent from the foregoing that there is a need in the art for therapeutic/prophylactic methods for metabolic syndrome. Exemplary, therapeutic/prophylactic methods will treat or prevent several symptoms of metabolic syndrome.
Obesity
The incidence of obesity has increased dramatically throughout the world, most notably over the last 3 decades. By the year 2000, a total of 38.8 million American adults or 30% of the population of that country were classified as obese (i.e., having a body mass index score of at least 30 kg/m2 for Caucasians, 25 kg/m2 for Japanese and 28 kg/m2 for Chinese). Obesity is associated with or thought to cause a number of diseases or disorders, and estimates attribute approximately 280,000 deaths each year in the United States to obesity related disorders.
Obesity is a risk factor for developing many obesity-related complications, from non-fatal debilitating conditions, such as, for example, osteoarthritis and respiratory disorders, to life-threatening chronic disorders, such as, for example, hypertension, type 2 diabetes, atherosclerosis, cardiovascular disease, some forms of cancer and stroke.
As the number of subjects that are obese is increasing (in the US alone the incidence of obesity increased one third in the last decade), the need to develop new and effective strategies in controlling obesity and obesity-related complications is becoming increasingly important.
Despite the high prevalence of obesity and many advances in our understanding of how it develops, current therapeutic strategies have persistently failed to achieve long-term success. Moreover, of the subjects that do lose weight, approximately 90 to 95 percent of subsequently regain their lost weight.
There are currently few therapeutic drugs approved by the FDA for the long term treatment of obesity. One of these compounds, orlistat, is a pancreatic lipase inhibitor that acts by blocking fat absorption into the body. However, the use of this drug is also accompanied by the unpleasant side effects of the passage of undigested fat from the body.
Another drug commonly used for the treatment of obesity is sibutramine, an appetite suppressant. Sibutramine is a β-phenethylamine that selectively inhibits the reuptake of noradrenaline and serotonin in the brain. Unfortunately, the use of sibutramine is also associated with elevated blood pressure and increased heart rate. As a result of these side effects dosage of sibutramine is limited to a level that is below the most efficacious dose.
Compounds for the short term treatment of obesity include, appetite suppressants, such as amphetamine derivatives. However, these compounds are highly addictive. Furthermore, subjects respond differently to these weight-loss medications, with some losing more weight than others and some not losing any weight whatsoever.
It will be apparent to the skilled artisan based on the foregoing, that there is a need in the art for methods of treating or preventing obesity or reducing body weight.